The overall goal of our PPG is to better understand the synergy between environmental stress, adiposity, and impaired sodium regulation in the development of hypertension in high risk populations. Three projects are proposed supported by three Cores (Administrative, Bioassay, Biostatistics). Each of the three projects we propose has a unique focus, but they also have commonalities across the projects. The high synergy and integration allows us to apply information gained from one project to the understanding of the results of another. All three projects hypothesize a central role for SNS-induced changes in Ang II as a mediator of impaired functioning. In addition, all three projects will focus on understanding the physiological mechanisms through which stress and obesity contribute to hypertension in African Americans. Projects 1 and 3 will examine different pathways in human and animal models. Specifically, Project 1 hypothesizes Ang II is one factor responsible for sodium retention during stress in African Americans which leads to the early development of hypertension. These studies are complimented by Project 3 that will focus on the ETB receptor and use in whole body sodium retention. Project 2 will examine the impact of early life stress on Ang H-related functioning of the immune system and the development of hypertension in animal models. This stimulated Project 1 to explore this relationship in our human model of hypertension in African Americans. Projects 2 and 3 will both examine factors related to endothelial function in different models of obesity-related disease. Taken together, there is strong synergy between the projects that will allow us to identify critical factors in obesity and stress-related hypertension. More importantly, they will allow us to identify the mechanisms underlying the synergistic effect of obesity on stress-related hypertension.